Identification of target regions for CKD therapy among the molecular structure of (pro)renin receptor.

• Project/Area Number: 25293198
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Kidney internal medicine
• Research Institution: Tokyo Women's Medical University
• Principal Investigator: Ichihara Atsuhiro 東京女子医科大学, 医学部, 教授 (60203105)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥18,590,000 (Direct Cost: ¥14,300,000、Indirect Cost: ¥4,290,000); Fiscal Year 2015: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000); Fiscal Year 2014: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000); Fiscal Year 2013: ¥6,890,000 (Direct Cost: ¥5,300,000、Indirect Cost: ¥1,590,000)
• Keywords: 慢性腎臓病 / 老化 / 骨格筋 / サルコペニア / サルコぺニア / 細胞内pH / V-ATPase / furin

Outline of Final Research Achievements

Rescue experiments using fragments of the (P)RR gene in (P)RR-deficient MEF showed the essential role of the (P)RR extracellular domain in maintenance of cell life. However, once V-ATPase is constructed, processing of the full length (P)RR to the extracellular (P)RR domain is not always necessary for the construction of V-ATPase. In addition, the mice overexpressed soluble (P)RR, that is almost extracellular domain of (P)RR, had no abnormal phenotype. Whereas, the mice overexpressed full-length (P)RR had fast muscle-dominant muscle atrophy mimicked human sarcopenia. The mechanism involved molecules contributing to autophagy, Wnt signals, and Sirt1.

Research Products

• [Journal Article] Placental (pro)renin receptor expression and plasma soluble (pro)renin receptor levels in preeclampsia (2016)
  • Author(s): T Narita, A Ichihara, K Matsuoka, Y Takai, K BOkuda, S Morimoto, H Itoh, H Seki
  • Journal Title: Placenta Volume: 37 Pages: 72-78
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] A functional (pro)renin receptor is expressed in human lymphocytes and monocytes. (2015)
  • Author(s): Narumi K, Hirose T, Sato E, Mori T, Kisu K, Ishikawa M, Totsune K, Ishii T, Ichihara A, Nguyen G, Sato H, Ito S.
  • Journal Title: Am J Physiol Renal Physiol. Volume: 308 Issue: 5 Pages: F487-F499
  • DOI: 10.1152/ajprenal.00206.2014
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] (Pro)renin receptor is crucial for Wnt/β-catenin-dependent genesis of pancreatic ductal adenocarcinoma. (2015)
  • Author(s): Shibayama Y, Fujimori T, Nguyen G, Hirose T, Totsune K, Ichihara A, Kitada K, Nakano D, Kobori H, Kohno M, Masaki T, Suzuki Y, Yachida S, Nishiyama A.
  • Journal Title: Scientific Reports Volume: 5 Issue: 1 Pages: 8854-8854
  • DOI: 10.1038/srep08854
  • Peer Reviewed / Open Access
• [Journal Article] Prediction of gestational diabetes mellitus by soluble (pro)renin receptor during the first trimester (2013)
  • Author(s): Watanabe N, Morimoto S, Fujiwara T, Suzuki T, Taniguchi K, Mori F, Ando T, Watanabe D, Kimura T, Sago H, Ichihara A.
  • Journal Title: J Clin Endocrinol Metab Volume: ９８ Issue: 6 Pages: 2528-2535
  • DOI: 10.1210/jc.2012-4139
  • Peer Reviewed
• [Journal Article] The role of individual domains and the significance of shedding of ATP6AP2/(pro)renin receptor in vacuolar H+-ATPase biogenesis (2013)
  • Author(s): Kinouchi et al
  • Journal Title: Plos One Volume: 8 Issue: 11 Pages: e78603-e78603
  • DOI: 10.1371/journal.pone.0078603
  • Peer Reviewed